Artesunate targets cellular metabolism to regulate the Th17/Treg cell balance

Inflamm Res. 2023 May;72(5):1037-1050. doi: 10.1007/s00011-023-01729-9. Epub 2023 Apr 6.

Abstract

Introduction: Metabolic reprogramming is one of the important mechanisms of cell differentiation, and different cells have different preferences for energy sources. During the differentiation of naive CD4 + T cells into Th17 and Treg cells, these cells show specific energy metabolism characteristics. Th17 cells depend on enhanced glycolysis, fatty acid synthesis, and glutaminolysis. In contrast, Treg cells are dependent on oxidative phosphorylation, fatty acid oxidation, and amino acid depletion. As a potent antimalarial drug, artesunate has been shown to modulate the Th17/Treg imbalance and regulate cell metabolism.

Methodology: Relevant literatures on ART, cellular metabolism, glycolysis, lipid metabolism, amino acid metabolism, CD4 + T cells, Th17 cells, and Treg cells published from January 1, 2010 to now were searched in PubMed database.

Conclusion: In this review, we will highlight recent advances in which artesunate can restore the Th17/Treg imbalance in disease states by altering T-cell metabolism to influence differentiation and lineage selection. Data from the current study show that few studies have focused on the effect of ART on cellular metabolism. ART can affect the metabolic characteristics of T cells (glycolysis, lipid metabolism, and amino acid metabolism) and interfere with their differentiation lineage, thereby regulating the balance of Th17/Treg and alleviating the symptoms of the disease.

Keywords: Amino acid metabolism; Artesunate; Cellular metabolism; Glycolysis; Lipid metabolism; Th17/Treg.

Publication types

  • Review

MeSH terms

  • Artesunate / metabolism
  • Artesunate / pharmacology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation
  • Fatty Acids / metabolism
  • T-Lymphocytes, Regulatory*
  • Th17 Cells* / metabolism

Substances

  • Artesunate
  • Fatty Acids